The central aim of this core is to provide optical imaging services to visualize and dissect CF relevant disease processes and assess therapeutic regimens at the cellular level. These studies will rely on a variety of cutting edge microscopic methods to support physiologic and molecular approaches to study airway dysfunction, injury and potential therapeutic interventions in cystic fibrosis (CF). As such, a central imaging core is defined as an integral component of this proposal. The Core will be housed in the Center for Biologic Imaging (CBI) of the University of Pittsburgh Medical Center. This Center is equipped to perform a continuum of optical methods including all types of microscopy essential to this Program. Light microscopic techniques include conventional histological, immuno-histological, laser-based confocal, and multiphoton imaging. Based upon our activity in the last grant period we will also provide extensive multiparametric ratiometric methods and live cell and tissue imaging technologies. Our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate subtle qualitative changes; a major function of the Core in this Program. At the electron microscopic level, thin section electron microscopy and immuno-electron microscopic evaluation of specimens is a natural extension of the light microscopic analyses and will be employed when needed. A second facet of core function is the development of novel optical imaging methods specifically for this program. This aspect of core function is described in detail in the preliminary data section. The CBI already has extensive established interactions with the project leaders and we expect these interactions to continue to expand within the formal rubric of this program